Fig. 4: EXT2 targeting alters the metabolome of GBM cells. | Cell Death & Differentiation

Fig. 4: EXT2 targeting alters the metabolome of GBM cells.

From: A novel role of exostosin glycosyltransferase 2 (EXT2) in glioblastoma cell metabolism, radiosensitivity and ferroptosis

Fig. 4

A Workflow of untargeted metabolomics upon EXT2 knockdown in irradiated DD-T4 and U-251MG cells. B Differential impact of the treatment groups on the metabolome of DD-T4 and U-251MG GBM models determined by Partial Least-Squares Discriminant Analysis (PLSDA) using MetaboAnalyst.ca web tool. C Filtration of LC-MS/MS analytical features for metabolite identification using Human Metabolome Data Base (HMDB) web tool. D Categorization of metabolite content by HMDB and determination of changes in metabolite abundance upon EXT2 depletion and irradiation. Numbers in column graph indicate significantly altered metabolites in the respective color-coded metabolite category. Data are visualized as mean (n = 4) of the fold change (relative to siC/IR). Significant alterations were determined by t-test with p < 0.05. E Identified deregulated metabolic pathways upon EXT2 knockdown and irradiation obtained from KEGG and Small Molecule Pathway Database (SMPDB) database analyses. The impact is quantified as a percentage of significant up- and down-regulated metabolites. F Overlap of significantly altered metabolites, shown in D in DD-T4 and U-251MG models. G SAM metabolite abundance in unirradiated and irradiated EXT2-depleted cell cultures. H Mapping of metabolites involved in SAM metabolism altered upon EXT2 knockdown identified from untargeted metabolomics. Color code: red, upregulated; blue, down-regulated; green, not changed; black, metabolite not found. Metabolite abundance indicates peak intensity value (n = 4; one-way ANOVA; **p < 0.01; ***p < 0.005).

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